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High-Sensitivity Cardiac Troponin Assays in U.S. Hospitals: A Report Card Free Access

Editorial Comment

J Am Coll Cardiol, 81 (3) 220–223
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Introduction

The emergence and clinical adoption of cardiac troponin (cTn) I and T assays over the past 3 decades has transformed the diagnosis of myocardial infarction (MI), allowing clinicians to confirm myocardial injury through direct biochemical detection of cardiomyocyte necrosis.1 Refinements in analytic technology in the late 2000s allowed for enhanced analytic performance of troponin assays, specifically the ability to detect substantially lower circulating concentrations of troponin.

Multiple clinical studies confirmed the superior diagnostic accuracy of the newer-generation “high-sensitivity” cardiac troponin (hs-cTn) assays,2,3 yet despite the robust evidence base supporting their use, adoption of hs-cTn assays in clinical practice has been slow in the United States compared with other countries, in part because they were not approved by the Food and Drug Administration until 2017.4 In addition, lingering concerns have remained about the potential impact of using hs-cTn assays on health care resource utilization owing to the inherent trade-off between their superior clinical sensitivity but diminished clinical specificity for the diagnosis of MI.5 Nevertheless, acknowledging the more accurate detection and exclusion of myocardial injury with hs-cTn assays, professional society guidelines have now fully embraced hs-cTn as the preferred standard for establishing a biomarker diagnosis of MI,1,6 in theory paving the way for their broader adoption into U.S. clinical practice. In this issue of the Journal of the American College of Cardiology, McCarthy et al7 report the largest observational study of hs-cTn assays in U.S. hospitals to date, focusing on recent trends in their implementation and the association of their use with in-hospital cardiac testing and outcomes. In doing so, they offer a report card for hs-cTn assays in U.S. hospitals, allaying some fears, raising new questions, and highlighting opportunities for continued quality improvement in the years ahead.

In their analysis, McCarthy et al7 examined patient-level data from >250,000 patients across 550 U.S. hospitals participating in the National Cardiovascular Data Registry Chest Pain–MI Registry from January 2019 to September 2021. An ongoing quality improvement initiative sponsored by the American College of Cardiology, the Chest Pain–MI Registry collects detailed clinical information about patients presenting with type 1 MI, unstable angina, and low-risk chest pain, but notably excludes patients with type 2 MI.8 The investigators further refined their cohort to exclude hospitals with limited or inconsistent reporting practices and to exclude patients with ST-segment elevation myocardial infarction or missing troponin data, among others.

What did the investigators find?

Regarding recent trends in use of hs-cTn assays, the investigators found that although implementation of hs-cTn among U.S. hospitals is increasing, the majority of U.S. hospitals continue to use less-sensitive conventional troponin assays. Based on a threshold of at least 25% of patients being evaluated with a hs-cTn assay at a given hospital to define implementation of hs-cTn at that facility, the investigators specifically reported that implementation of hs-cTn assays increased from 3.3% in Q1 2019 to 32.6% in Q3 2021 (Figure 1). As a benchmark, in a global survey of 1,902 medical centers in 23 countries conducted in 2016, the majority of respondents from Europe (60%) and Australia (55%) had already adopted hs-cTn assays.9 Thus, despite progress, the United States remains a significant outlier in hs-cTn utilization.

Figure 1
Figure 1

Use of hs-cTn Assays in the United States: 2019-2021

Increase in use of hs-cTn from January 2019 to September 2021. Comparison of the use of hs-cTn assays vs conventional troponin assays. hs-cTn = high sensitivity cardiac troponin; NSTEMI = non–ST-segment elevation myocardial infarction.

Regarding cardiac testing, there were 2 principal findings, with notable differences between the distinct subgroups of patients included in the analysis (ie, low-risk chest pain vs non–ST-segment elevation acute coronary syndromes [NSTE-ACS]). First, among low-risk chest pain patients, there was a significantly lower rate of invasive coronary angiography in patients evaluated with hs-cTn assays compared with those evaluated with conventional assays (3.7% vs 4.5%) (Figure 1). In addition, use of stress testing or CT coronary angiography was numerically lower in low-risk chest pain patients evaluated with hs-cTn assays (20.1% vs 24.6%), although this difference did not achieve statistical significance over the early initiation period examined. Collectively, these findings suggest that use of hs-cTn assays in U.S. hospitals may already be supporting one of its key potential promises, namely the ability to rapidly rule out MI in the emergency department without the need for additional ischemic evaluation. Indeed, the superior clinical sensitivity of hs-cTn assays implies a robust negative predictive value (NPV) for MI, which has led to the development and validation of multiple early rule-out strategies with the use of hs-cTn, often with guidance not to pursue additional diagnostic testing.10,11 Second, among patients ultimately characterized as having NSTE-ACS, there was greater use of echocardiography in those evaluated with the use of hs-cTn assays compared with those evaluated with conventional assays (82.4% vs 75.0%). Clinically speaking, the decision to pursue echocardiography in response to an elevated cardiac troponin value is often driven by a desire to distinguish between ischemic and nonischemic myocardial injury. Therefore, one potential interpretation of this observation is that detection of low levels of myocardial injury with the use of hs-cTn may be more likely to prompt echocardiography for diagnostic clarity.

Finally, regarding relevant clinical outcomes, the investigators observed a modest but significantly shorter length of stay both in patients with low-risk chest pain (5.8 hours vs 6.2 hours) and in those with NSTE-ACS (66.9 hours vs 67.8 hours) evaluated with hs-cTn assays (Figure 1). Although integration of hs-cTn into rapid rule-out strategies is likely to account for this trend in the low-risk group, the consistent finding in patients with NSTE-ACS suggests that even rapid rule-in strategies may translate to more expeditious use of invasive coronary angiography and revascularization, and ultimately to more efficient disposition planning. There was no difference in risk of in-hospital mortality between patients evaluated with the use of hs-cTn vs conventional assays, though it bears reminding that the theoretical concern with rapid rule-out protocols leveraging hs-cTn assays is the risk of prematurely discharging a patient who has not yet manifested myocardial injury. Because the Chest Pain–MI Registry does not capture postdischarge outcomes, this question could not be addressed in this analysis.

In presenting their findings, the investigators correctly point to the uncertainty introduced by the exclusion of patients with type II MI, a group defined as having acute myocardial injury in the clinical context of myocardial ischemia due to myocardial oxygen supply-demand mismatch rather than coronary atherothrombosis.1 In addition, the classification of clinical syndromes in the Chest Pain–MI Registry does not lend itself to easily identifying patients with acute nonischemic myocardial injury, who may be represented to some extent in the low-risk chest pain subgroup but are more likely to be excluded altogether from the registry. Previous studies have suggested that diagnoses of both type 2 MI and acute nonischemic myocardial injury may be more common with the use of hs-cTn assays,12,13 so their exclusion from the denominator of the present analysis makes it challenging to fully characterize the cascades of resource utilization that might arise from hs-cTn use. In a surprising finding, the authors found that patients evaluated with hs-cTn assays compared with conventional troponin assays had a slightly higher proportion of unstable angina diagnoses (7.1% vs 6.3%) and a correspondingly lower proportion of non–ST-segment elevation MI diagnoses (61.1% vs 61.9%). Because hs-cTn assays are (by definition) better able to detect very low levels of myocardial injury, the fraction of NSTE-ACS patients without detectable MI (ie, unstable angina) should theoretically decrease with the use of hs-cTn assays, rather than increase as seen in this analysis.14

Where do we go from here?

Despite the potential limitations of their dataset, McCarthy et al’s7 analysis offers the largest and clearest picture yet of where we stand with hs-cTn assays in U.S. hospitals. Broadly speaking, adoption of hs-cTn assays has not been associated with excess resource utilization, and in some clinical scenarios may be having a favorable impact on cardiac testing. Although one might have optimistically hoped for more robust associations of ischemic testing and length of stay with the use of hs-cTn assays, it is important to remember that nearly all transitions to hs-cTn assays occurred during the <3-year study period, and that perhaps the health system benefits of hs-cTn use may accrue with more experience and greater comfort with interpretation of the assays. To this end, follow-up patient-level studies are needed to keep an eye on temporal trends.

Above all, the McCarthy et al7 work underscores the persistent implementation gap that is unfortunately all too common with novel cardiovascular technologies. It is our hope that reports like this shine a spotlight on this issue and motivate quality improvement efforts to more effectively implement hs-cTn in U.S. hospitals. As report cards go, there is definite room for growth and improvement in implementation, but also the need for continued evaluation.

Funding Support and Author Disclosures

Dr Gulati has served on an advisory board for Novartis; was a speaker for Siemens Healthcare Diagnostics; is a co-investigator and site principal investigator of the WARRIOR study funded by the Department of Defense; and is a co-investigator of the WISE study. Dr Berg is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women‘s Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences; has received consulting fees from AstraZeneca, Mobility Bio, and Youngene Therapeutics; has received honoraria from the Medical Education Speakers Network; and participates on clinical endpoint committees for studies sponsored by Kowa Pharmaceuticals.

References

Footnotes

Athena Poppas, MD, served as Guest Editor-in-Chief for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.